Hydrochloric Acid → 2-(Thieno[2,3-d]pyridazin-3-yl)furo[2,3-c]pyridin-7-amine

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Reaction Conditions

Reaction Steps

A suspension of {7-[bis(tert-butoxycarbonyl)amino]furo[2,3-c]pyridin-2-yl}boronic acid (200.0 mg, 0.5288 mmol), 3-bromothieno[2,3-d]pyridazine (77.1 mg, 0.358 mmol), Pd(PPh3)4 (21.8 mg, 0.0189 mmol), and potassium carbonate (150.5 mg, 1.089 mmol) in a 4:1 mixture of 1,4-dioxane to water (3.5 mL) was heated conventionally to 70° C. for 2.5 h. To the stirring reaction at 70° C., 4.0 M hydrochloric acid in 1,4-dioxane (2.0 mL) was added and was stirred for 1 h. The reaction mixture was cooled to ambient temperature, poured into saturated aqueous sodium bicarbonate, and extracted with dichloromethane. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. Purification by ISCO chromatography (3 to 15% methanol:dichloromethane) afforded 30.6 mg (31%) of the title compound as a yellow solid. 1H NMR (400 MHz, DMF-d7): δ 10.43 (d, J=1.52 Hz, 1H), 10.10 (d, J=1.52 Hz, 1H), 8.92 (s, 1H), 7.83 (d, J=5.31 Hz, 1H), 7.67 (s, 1H), 6.95 (d, J=5.31 Hz, 1H), 6.66 (br s, 2H); MS (ESI): 269.13 [M+H]+; HPLC tR=2.16 min.

Provenance & Evidence